Principal Investigator: Dr Guido J. R. Zaman
Partners: NTRC, NKI, UMCU

TTK (Mps1) is an activator of the mitotic checkpoint, which functions as a safeguard to ensure the accurate segregation of replicated sister chromatids to daughter cells during mitosis. Defects in the mitotic checkpoint result in a numerical aberration of chromosomes, called 'aneuploidy'. Aneuploidy is frequently detected in tumor cells and thus considered a hallmark of cancer. Based on results from the TI Pharma project 'Kinases in Cancer 1' the hypothesis was developed that impairment of the mitotic checkpoint through inhibition of TTK may sensitize tumor cells to treatment with the anti-cancer drug paclitaxel (taxol). In this follow up program, the value of this novel mechanism for the specific targeting of tumor cells will be investigated.

The synergistic effect of TTK inhibitors and taxanes will be investigated and expanded to a broad panel of tumor cell lines and diverse chemotherapeutic agents. The in vivo efficacy of TTK inhibitors, in the absence and presence of co-treatment with taxanes, will be tested in an advanced mouse model for mammary carcinoma.

Fast facts:
Full project title: Kinases in Cancer 2
Start date: 6-6-2012
End date: 31-12-2013
Goals: In vivo validation of the concept that chemical inhibition of TTK sensitizes tumor cells to treatment with taxanes.
Project budget: 2.2 M

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